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SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity.

ABSTRACT: C. elegans SET-9 and SET-26 are highly homologous paralogs that share redundant functions in germline development, but SET-26 alone plays a key role in longevity and heat stress response. Whereas SET-26 is broadly expressed, SET-9 is only detectable in the germline, which likely accounts for their different biological roles. SET-9 and SET-26 bind to H3K4me3 with adjacent acetylation marks in vitro and in vivo. In the soma, SET-26 acts through DAF-16 to modulate longevity. In the germline, SET-9 and SET-26 restrict H3K4me3 domains around SET-9 and SET-26 binding sites, and regulate the expression of specific target genes, with critical consequence on germline development. SET-9 and SET-26 are highly conserved and our findings provide new insights into the functions of these H3K4me3 readers in germline development and longevity.

SUBMITTER: Wang W

PROVIDER: S-EPMC6010342 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity.

Wang Wenke W Chaturbedi Amaresh A Wang Minghui M An Serim S Santhi Velayudhan Satheeja S Lee Siu Sylvia SS

eLife 20180501

<i>C. elegans</i> SET-9 and SET-26 are highly homologous paralogs that share redundant functions in germline development, but SET-26 alone plays a key role in longevity and heat stress response. Whereas SET-26 is broadly expressed, SET-9 is only detectable in the germline, which likely accounts for their different biological roles. SET-9 and SET-26 bind to H3K4me3 with adjacent acetylation marks in vitro and in vivo. In the soma, SET-26 acts through DAF-16 to modulate longevity. In the germline, ...[more]

PMID: 29714684

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SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity

Project description:SET-9 and SET-26 are highly homologous paralogs that share redundant function in germline development, but SET-26 alone plays a key role in longevity and heat stress response. SET-26 is broadly expressed, but SET-9 is only detectable in the germline, which likely account for their different biological roles. SET-9 and SET-26 bind to H3K4me3 in vitro and in vivo, and their loss results in broadening of H3K4me3 domains. SET-9 and SET-26 also regulate the RNA expression of a subset of their target genes, irrespective of their H3K4me3 status. We propose that SET-9 and SET-26 function to organize local chromatin environment and to regulate the expression of specific target genes, and these activities together contribute to their critical roles in germline development, stress response, and longevity. SET-9 and SET-26 are highly homologous to human MLL5, a factor implicated in leukemia and glioblastoma, and our findings help to provide new insights into MLL5.

2018-05-31 | GSE108848 | GEO

SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity

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Sperm-carried RNAs play critical roles in mouse embryonic development.

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Histone methyltransferases MLL2 and SETD1A/B play distinct roles in H3K4me3 deposition during the transition from totipotency to pluripotency

Project description:In early mammalian embryogenesis, a shift from non-canonical histone H3 lysine 4 trimethylation (H3K4me3) linked to transcriptional repression to canonical H3K4me3 indicating active promoters occurs during zygotic genome activation (ZGA). However, the mechanisms and roles of these H3K4me3 states in embryogenesis remain poorly understood. Our research reveals that the histone methyltransferase MLL2 is responsible for installing H3K4me3 (both non-canonical and canonical) in totipotent embryos, while a transition to SETD1A/B-deposited H3K4me3 occurs in pluripotent embryos. Interestingly, MLL2-mediated H3K4me3 operates independently of transcription, fostering a relaxed chromatin state conducive to totipotency rather than directly influencing transcription. Conversely, SETD1A/B-mediated H3K4me3, which depends on transcription, is crucial for facilitating expression of genes essential for pluripotency and pre-implantation development. Our findings highlight the role of the H3K4me3 transition, mediated by an MLL2-to-SETD1A/B relay mechanism, in the regulation of transition from totipotency to pluripotency during early embryogenesis.

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Widespread PRC barrel proteins play critical roles in archaeal cell division.

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